Fibromyalgia (FM) is a chronic pain disorder defined by widespread musculoskeletal pain, persistent fatigue, and difficulties with cognitive function, often called “fibro fog.” The condition is not a disease of the muscles or joints, but rather a disorder involving how the central nervous system processes pain signals. FM is understood to be a state of generalized pain hypersensitivity, where the brain and spinal cord amplify sensory input. This altered pain perception forms the basis for the debilitating symptoms experienced by affected individuals.
The Role of Central Sensitization
Central sensitization is considered the primary mechanism driving the chronic widespread pain of fibromyalgia. This process involves the hyperexcitability of neurons within the spinal cord and the brain, essentially turning up the “volume knob” for pain perception permanently. Normal sensory input that should not cause discomfort is mistakenly interpreted as painful, a phenomenon known as allodynia. Stimuli that are normally mildly painful elicit a severely exaggerated response, which is called hyperalgesia.
The central nervous system becomes persistently over-responsive to both painful and non-painful signals. This heightened state is maintained by ongoing changes in the strength of connections between neurons, making them fire more readily. Neurons in the dorsal horn of the spinal cord become sensitized, requiring far less stimulation to signal pain to the brain. This amplification means that even light touch or pressure can activate pain pathways, resulting in the characteristic tenderness and diffuse body aches of FM.
The sustained hyperexcitability of these central neurons also causes an expansion of their receptive fields. Normally, a neuron responds only to input from a specific, localized body area, but in central sensitization, it begins to respond to input from adjacent areas. This change contributes to the widespread nature of the pain, as a stimulus in one area can trigger pain in a much broader region. Functional neuroimaging studies confirm this alteration, showing that brain regions involved in pain processing are hyperactive in individuals with FM.
Neurotransmitter Dysregulation
Chemical imbalances in the central nervous system contribute significantly to the development and maintenance of central sensitization. Specific pain-exciting and pain-inhibiting neurotransmitters are dysregulated, disrupting the brain’s ability to modulate pain signals effectively. The descending pain inhibitory pathways, which normally release chemicals to dampen ascending pain messages, function poorly. This dysfunction is linked to reduced levels of key pain-inhibiting neurotransmitters, specifically serotonin and norepinephrine, in the spinal cord and brain.
Serotonin and norepinephrine dampen pain signals traveling through the spinal cord. Lower concentrations of these chemicals weaken the body’s natural braking system for pain, allowing signals to pass through unchecked and amplified. Conversely, levels of pain-exciting neurotransmitters, such as Substance P and glutamate, are often elevated in the cerebrospinal fluid of FM patients. Substance P, a neuropeptide involved in nociception, has been measured at levels up to three times higher than normal in some studies.
Glutamate is a primary excitatory neurotransmitter that plays a role in pain signaling and the hyperexcitability of central neurons. Elevated glutamate levels are observed in pain-processing brain regions like the insula and cingulate cortex, correlating with heightened pain sensitivity. Both glutamate and Substance P activate N-methyl-D-aspartate (NMDA) receptors, which strengthen synaptic connections and contribute to sustained neuronal hyperexcitability. This chemical shift creates an environment where excitatory signals dominate, leading to persistent, widespread pain.
Immune System Contribution
While fibromyalgia is not an inflammatory or autoimmune disease in the traditional sense, research indicates a role for immune system involvement and low-grade neuroinflammation. This neuroinflammation stems from the abnormal activation of non-neuronal cells in the central nervous system, particularly glial cells. Glial cells, which include microglia and astrocytes, are the immune cells of the brain and spinal cord that typically maintain a healthy neuronal environment.
In FM, these glial cells become activated, promoting inflammation within the nervous system. Activated microglia and astrocytes release various pro-inflammatory chemicals, known as cytokines, such as Interleukin-6 (IL-6), Interleukin-8 (IL-8), and Tumor Necrosis Factor-alpha (TNF- \(\alpha\)). These cytokines interfere with normal neuronal function and contribute directly to enhanced pain signaling and cognitive difficulties, or “brain fog,” characteristic of FM.
The continuous release of these inflammatory mediators exacerbates the central sensitization process. Substance P can stimulate glial cell activation, creating a self-perpetuating cycle where heightened pain signals encourage more neuroinflammation. This localized inflammation in the brain and spinal cord lowers the pain threshold, making the nervous system more sensitive to incoming stimuli.
Genetic and Environmental Predisposition
The development of fibromyalgia often requires a combination of underlying vulnerability and external initiating factors. Genetic predisposition plays a notable role, with familial studies estimating that genetic factors may account for up to 50% of an individual’s susceptibility. FM tends to aggregate in families, and first-degree relatives of affected individuals have an increased risk of developing the syndrome.
This genetic risk is likely polygenic, involving variations in multiple genes rather than a single “fibromyalgia gene.” Many candidate genes regulate neurotransmitters, particularly those related to the serotonergic, dopaminergic, and catecholaminergic systems that manage pain and stress response. For example, polymorphisms in the gene for catechol-O-methyltransferase (COMT), an enzyme that degrades norepinephrine and dopamine, are associated with altered pain sensitivity.
Environmental triggers act as initiating events, particularly in individuals with genetic susceptibility. These triggers often involve significant stressors that overwhelm the body’s regulatory systems, such as physical trauma from accidents or surgery. Severe infections, including certain viral illnesses, and profound psychological stress or post-traumatic stress disorder (PTSD) have also been identified as triggers. These events initiate the cascade of neurological and chemical changes that lead to the establishment of central sensitization and chronic symptoms.